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Investigation of Solubility Enhancement Approaches of Ticagrelor
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ABSTRACT

                   Ticagrelor is an orally administered antiplatelet medicine, direct-acting P2Y12-receptor antagonist. Ticagrelor binds reversibly and noncompetitively to the P2Y12 receptor at a site distinct from that of the endogenous agonist adenosine diphosphate (ADP). Inhibition of platelet aggregation stimulated by ADP is a commonly used pharmacodynamic parameter for P2Y12-receptor antagonists.

                  Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10?g/mL at room temperature. Ticagrelor exhibits no pKa value within the physiological range. Ticagrelor does not exhibit pH-dependent solubility and is defined as ‘low solubility low permeability’ under the Biopharmaceutics Classification System (Class IV). The mean absolute bioavailability of ticagrelor in healthy volunteers is 36 %

                   Nanoparticles preparation and complexation is one of the recently used approaches to enhance the solubility of drugs. The aim of the present work was to improve the solubility and dissolution of ticagrelor by preparing nanoparticles and cyclodextrin inclusion complex of ticagrelor and then incorporated in to tablet dosage form. Fifteen formulas of nanoparticles were prepared by antisolvent precipitation method (solvent displacement method) utilizing one of the three polymers (PVP, Poloxamer, and HPMC) at three different drugs: polymer and solvent: anti-solvent ratios and nine formulas of cyclodextrin inclusion complex with HP?CD  by three preparation methods, physical trituration, kneading and solvent evaporation, which increase the solubility and dissolution rate of ticagrelor via formation of inclusion complex with HP?CD.

              The prepared formulas were characterized regarding the saturated solubility, polydispersity index, particle size by nano laser particle size analyzer, % yield, entrapment efficiency, and flowability, FTIR, DSC, and SEM. The selected formulas were prepared as tablets.

             The prepared tablets were evaluated for drug content, weight variation, hardness, and friability. In vitro dissolution data of the prepared tablets were analyzed using similarity factor (f2) and dissolution efficiency (DE).  

           Among all the prepared nanoparticles formulas, formula (F12) which contain HPMC as a polymer at polymer: drug ratio of (1:1) and solvent: antisolvent ratio of (1:1) was considered as the optimum formula which shows good evaluation parameters in addition to the increment in the solubility to about 9 times than that of the pure drug. The nanoparticle of the selected formula (F12) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 88 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  Moreover, the analysis by DSC and SEM of the nanoparticles of the selected formula (F12) indicate a reduction in the crystallinity and amorphization of the drug. It can be concluded that the selected formula is a promising formula for the preparation of ticagrelor nanoparticles the incorporation in a tablet dosage form.

          Regarding ticagrelor inclusion complex with HP?CD Solvent evaporation method was the most effective method regarding ticagrelor solubilization and optimum formula of inclusion complex (F23) show increment in saturated solubility about ten times that of pure drug.

          The ticagrelor inclusion complex of the selected formula (F23) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 90 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  

 

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Publication Date
Thu Feb 01 2018
Journal Name
Iosr Journal Of Pharmacy And Biological Sciences
Histopathological Study about effect of T.verrucosum on skin of the rabbits and treated by yellow sap and gel of Aloe vera
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Background : The dermatophytesare taxonomically related fungi causing different skin infections referred to as tineas in man or ringworm in man and animals . Objective:This study was established to investigate theof effect of yellow sap and gel of Aloe vera on skin of the rabbits which infected with T.verrucosum. Methods : Twelveskin biopsy were taken from rabbits for histopathological study to know the the effects of the T.verrucosumand treated with yellow sap and gel. Results : the results of histopathological study of effect of yellow sap and gel of Aloe vera on skin of the rabbits which infected with T.verrucosum showed the concentration of the gel of aloe vera at 75% was more effected to treat the infective area of skin with T.verrucos

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Publication Date
Wed Sep 20 2023
Journal Name
Scientific Culture
THE REALITY OF THE PARTICIPATION OF FEMALE ENTREPRENEURS IN ACHIEVING THE GOALS OF SUSTAINABLE DEVELOPMENT/ A FIELD STUDY IN BAGHDAD GOVERNORATE
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Abstract In light of the changing conditions that prevail in society, and the intense competition that institutions and countries are forced to face, especially after the opening of markets, and the transformation of the world into what is called a small village, entrepreneurship has emerged as an important tool for dealing with the developments of societies, whether it is related to individual business projects or Economics for national business, leadership was the key to any driving force towards achieving growth. Today, women are no longer captive to a specific orientation, but rather all horizons and fields of work have been opened to them, and they have been able to occupy the most important economic, voluntary, service, and

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Publication Date
Mon Feb 18 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Role of the financial Statements in Achieving of the Banking Supervision: An Applied Study in A sample of Iraqi Banks
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Banks are considered the main basis of financial sector ,so they must be submitted to sound and strict regulatory system and so as to ensure their operations and according to instructions and regulations , in order to maintain the integrity of the banking sector and financial sector in general .One of the importance regulatory tools that are adopted by the Iraqi Central Bank to control over the banks an financial and periodic statements that are provided by the banks in accordance with planned schedules .The financial statements of the banks must reflect clearly and accurately financial situation and the result of their activities during the period in which they represent to achiveing its purposes.So it has the goal of Search is statemen

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Publication Date
Wed Dec 28 2022
Journal Name
Al–bahith Al–a'alami
Interactivity of iraqi daily newspapers sites an analytical study of the websites of al-mada,al-zaman.al-sabahand tareqal-shaab newspapers
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A study of interactivity in the Iraqi newspaper sites_ An analytical study of the website of Al-Mada, Al-Zaman, Al-Sabah and Tariq Al-Shaab newspaper sought to determine the amount of interactivity in the sites of Iraqi newspapers that have been published since 2003, which consists of (15) newspapers according to the statistics of the Iraqi Books and Documents House.

and the researcher conducted an analytical survey on these sites, and the percentage of interactivity in general was weak, not more than (47.1%), and this weakness in interactivity contributed greatly to the decline in surfers of the websites of those electronic newspapers.

The highest aggregate rate of the research sample was in the simple interactive tools

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Publication Date
Thu Feb 06 2020
Journal Name
Political Sciences Journal
Self-immuniztion: integration of Russian strategic performance a study in the geopolitical orientation circles "of the stage of president putin"n
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In the period after the collapse of the Soviet Union in 1991, the Federal Republic of Russia witnessed a setback in the overall strategic performance of the country, as it went through a stage of performance flop between the orientation towards Europe in the era of President Boris Yelsen (1991-1999), or the change of direction towards Eurasia, as the Russian Federation managed After President Vladimir Putin assumed power in 2000, from rebuilding the same state and preserving national unity and social cohesion, as well as building a phased military doctrine that made clear moves in Russian strategic thought and future directions towards regions of eternal importance in Russian strategic perception Lack of a set of motivations based on it:

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Publication Date
Mon Dec 23 2019
Journal Name
Opcion
The Effect Of Employing The Strategy Of The TalkativeGroups On The Achievement And Attitudes Of ChemistryFor Fifth Grade Students Applied Scienc
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The study aimed to reveal the impact of employing the strategy of the talk-ative groups on the achievement and academic tendencies of chemistry forstudents of the fifth grade of applied science for the academic year (2018 -2019), and to achieve this goal the researcher used the experimental methodon the sample of the study consisting of (50) students, prepared achievementtest falls Under (60) paragraphs, and the scale of tendencies for chemistryfalls under (30) paragraphs, and after the researcher completed the researchexperiment according to what was planned:The superiority of the experimental group studied according to the strate-gy of the talkative groups was found in the post-application of the test ofachievement and attitudes of chemis

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Publication Date
Sun Feb 05 2023
Journal Name
مجلة تكريت للعلوم الادارية والاقتصادية
The role of strategic auditing of human resources management in crystallizing organizational capabilities: A prospective study at the University of Baghdad
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دور التدقيق الاستراتيجي لإدارة الموارد البشرية في بلورة القدرات التنظيمية دراسة استطلاعية في رئاسة جامعة بغداد

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Publication Date
Mon Oct 06 2025
Journal Name
Journal Of Physical Education
The Effect Of Psychological Counselling On The Development Of Psychological Skills and the Level Of First Class Soccer Referees (Baghdad governorate)
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Publication Date
Thu Jan 17 2019
Journal Name
Energy Procedia
Irradiation of the thin films of MnS with fast neutrons and the possibility of using the new characteristics in optical detector
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The optical detectors which had been used in medical applications, and especially in radioactive treatments, need to be modified studied for the effects of radiations on them. This study included preparation of the MnS thin films in a way that vacuum thermal evaporation process at room temperature 27°C with thickness (400+-10nm) nm and a sedimentation rate of 0.39nm/sec on glass floors. The thin films prepared as a detector and had to be treated with neutron irradiation to examine the results gained from this process. The results decay X-ray (XRD) showed that all the prepared thin films have a multi-crystalline structure with the dominance of the direction (111), the two samples were irradiated with a neutron irradiation source (241Am-9Be)

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of the Role of Interleukein-2 and Interleukein-4 in the Immunopathogenesis of Steroid Therapy Resistance in Iraqi Asthmatic Patients
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Interleukins (IL-2 and IL-4) are increased in asthmatics and were reported to induce resistance to steroid therapy in some patients who fail to get benefit from glucocorticoids when used in full dose and for long period of time. In this context, the present study was conducted on Iraqi patients to provide additional laboratory mean, beside the clinical diagnosis, for the decision whether the asthma is steroid sensitive or resistant by monitoring the level of immunoglobulins, complement proteins and interleukins among asthmatic patients (steroid sensitive or resistant) and the possible contribution of other factors like age, sex and environments in the development of steroid resistance. A total number of 55 asthmatics and 28 normal subjec

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